Relationship Between NF-κB And JNK Gene Polymorphisms And Prognosis Of Nasopharyngeal Carcinoma

Objective: The aim of this study is to investigate the correlation between single nucleotide polymorphisms(SNPS)of NFKBIA,TRAF2,TRAF3,CHUK and MAP2K4 genes in the NF-κB and JNK signaling pathways and the survival prognosis of nasopharyngeal carcinoma.To find the genetic markers that can affect the overall survival(OS)and progression-free survival(PFS)of patients with nasopharyngeal carcinoma(NPC),and to comprehensively evaluate the risk factors affecting the prognosis of patients with NPC in advance,so as to guide clinicians to carry out early monitoring,active treatment and close follow-up of NPC population,and try to improve the OS and PFS of patients with NPC.Methods: A total of 178 patients with nasopharyngeal carcinoma confirmed by pathological biopsy in Sichuan Cancer Hospital from January 2017 to December 2018 were enrolled.In this study,13 single nucleotide polymorphisms(SNPS)of NFKBIA,TRAF2,TRAF3,CHUK and MAP2K4 genes in the NF-κB and JNK signaling pathways were selected,and the SNPS were genotyped by mass spectrometry.Kaplanmeier method was used to calculate overall survival(OS)and progression-free survival(PFS).log-rank test was used for univariate analysis between groups,and COX proportional hazards regression was used for multivariate analysis.To investigate the correlation between single nucleotide polymorphisms(SNPS)of NFKBIA,TRAF2,TRAF3,CHUK and MAP2K4 genes and the survival prognosis of nasopharyngeal carcinoma(NPC).Results: At a median follow-up of 52.4 months for all the patients in this study,50 had progression and 14 died.The overall survival(OS)and progression-free survival(PFS)rates were 92% and 72%,respectively.Multivariate analysis showed that NFKBIA(rs2273650)and MAP2K4(rs4792219)were independent prognostic factors for OS.In NFKBIA gene rs2273650,CT and TT genotypes had a 45.357 times higher risk of death than CC genotype(P=0.004,HR=45.357).AA and GA genotypes of rs4792219 in MAP2K4 gene had 7.452 times higher risk of death than GG genotype(P=0.023,HR=7.452).NFKBIA(rs2273650)and TRAF3(rs2075771)were independent prognostic factors for PFS.The CC genotype of NFKBIA(rs2273650)was a protective factor for progression-free survival,and the risk of progression of CT and TT genotypes was 1.975 times that of CC genotype(P=0.042,HR=1.975).The CT genotype of TRAF3(rs2075771)was a protective factor for progression-free survival,and the risk of progression of CC and TT genotypes was 2.122 times higher than that of CT genotype(P=0.046,HR=2.122).Conclusion: NFKBIA(rs2273650)and MAP2K4(rs4792219)were independent prognostic factors for overall survival,and NFKBIA(rs2273650)and TRAF3(rs2075771)were independent prognostic factors for progression-free survival.These SNPS may serve as genetic markers for predicting the survival and prognosis of NPC.Multi-center,larger sample size and further functional experiments are needed to confirm the results.